Active clinical trials for "Malaria"

Burkitt lymphoma (BL) is an aggressive monoclonal B-cell malignancy that is rare (sporadic) worldwide, but is 100-fold more common (endemic) in equatorial Africa, particularly among children. Epstein-Barr virus (EBV) and malaria are epidemiologically linked to endemic BL in epidemiologic studies, but questions remain about role of EBV variants and the evidence for association with malaria is weak. EBV is ubiquitous, yet only few children develop BL, possibly because only a few EBV variants are pathogenically relevant. The association of BL with malaria is based on ecologic and non-comparative clinical studies. Two case-control studies have reported significant association of high anti-malarial antibodies with BL (OR=5_ among children in Uganda and in Malawi, but selection bias (cases and controls came from dissimilar geographical areas) and reverse causality bias were limitations. Three studies were conducted in the 1960s and 70s to test association of carriage of malaria-resistance gene with BL, two of which reported a significant or marginal inverse association. These pioneering studies were small (240 cases all together) and looked at one polymorphism in one gene (sickle cell gene). Improvements in technologies to characterize genetic variation allow the EBV and malaria hypotheses to be examined with greater power by looking at genetic variation across multiple genes. Epidemiology of Burkitt lymphoma in East African children and minors (EMBLEM) is a case-control study of 1500 BL cases and 3000 age-, sex- and residence-frequency matched controls we are proposing to conduct in East Africa. The study will enroll cases at four hospitals in four regions in East Africa, where malaria transmission is holoendemic and year round. The controls will be enrolled from general population attendees at Health Center II (HC-II) units where the cases originated. The primary study objectives are: 1) to test the hypothesis that genetic resistance to malaria is associated with a lower risk of BL, and 2) to use genome-wide association methods to discover genetic variation that may be associated with decreased or increased risk of BL. Because genetic variation conveys no information on actual exposure to malaria or EBV, in secondary analyses, we will use empiric epidemiological questionnaire and laboratory methods: a) to measure exposure to malaria and its association with BL, and b) to measure EBV variants and their association with BL. To examine issues related to bias and to obtain data to correct for deviations, we will also enroll 2250 population controls from 5% of the villages to obtain population distribution of key exposures variables. This data will be used to reweight the distribution in HC-II controls back to the general population. ...

The purpose of this study is to determine the importance of key blood group molecules in the clinical outcome of Plasmodium falciparum malaria infection in children.

Rural communities involved in agriculture are often at highest risk of insect-borne diseases in Southeast (SE) Asia. Skin-applied insect repellents may prove a useful means of reducing mosquito-borne diseases for those people working outdoors in high risk areas. This trial is evaluating the use of insect repellent (20% diethyltoluamide) to reduce incidence of malaria, Japanese Encephalitis and Dengue. The investigators will recruit up to 1000 households from 100 villages in rural Laos. In each house the investigators shall recruit up to 5 individuals. Half of households will be randomised to repellent, half to a placebo. All individuals will be provided with insecticide treated bed nets for use at night. All household occupants will be followed for 7 months to record malaria cases by Rapid Diagnostic Test every month. Blood spots will be collected at start and end of study to measure Japanese Encephalitis and Dengue. All positive cases will be promptly treated. Outcome will be reduction in number of malaria cases (primary outcome) and Dengue/Japanese Encephalitis (secondary outcomes).

This study, conducted by the Malaria Research and Training Center at the Faculty of Medicine in Bamako and the NIAID will measure the frequency of occurrence of malaria in infants in Bancoumana, Mali. Information from the study will help in planning trials of malaria vaccines. Healthy children from 6 weeks to 6 months of age who live in the Bancoumana health area may be eligible for this study. Candidates are screened with a physical examination and blood tests. Participating children are visited at home for a total of about 17 visits to see if they are well. They come to the clinic every month during the 7-month study for a clinical evaluation, including a blood sample obtained by finger prick to test for malaria. Some of the blood collected may be stored and used for research. Children who become sick with malaria are treated for the disease.

Clinical pneumonia is a leading cause of pediatric hospitalization. The etiology is generally bacterial or viral. Prompt and optimal treatment of pneumonia is critical to reduce mortality. However, adequate pneumonia management is hampered by: a) the lack of a diagnostic tool that can be used at point-of-care (POC) and promptly and accurately allow the diagnosis of bacterial disease and b) lack of a prognostic POC test to help triage children in need of intensive assistance. Antibiotic therapy is frequently overprescribed as a result of suspected bacterial infections resulting in development of antibiotic resistance. Conversely, in malaria-endemic areas, antibiotics may also be "underprescribed" and children with bacterial pneumonia sent home without antibiotic therapy, when the clinical pneumonia is mistakenly attributed to a co-existing malaria infection. The investigators previously identified combinations of protein with 96% sensitivity and 86% specificity for detecting bacterial disease in Mozambican children with clinical pneumonia. The investigators' prior work showed that it is possible to identify biosignatures for diagnosis and prognosis using few proteins. Recently, other authors also identified different accurate biosignatures (e.g., IP-10, TRAIL and CRP). In this study, the investigators propose to validate and improve upon previous biosignatures by testing prior combinations and seeking novel combinations of markers in 900 pediatric inpatients aged 2 months to 5 years with clinical pneumonia in The Gambia. The investigators will also use alternative case criteria and seek diagnostic and prognostic combination of markers. This study will be conducted in Basse, rural Gambia, in two hospitals associated with the Medical Research Council Unity The Gambia (MRCG). Approximately 900 pediatric patients with clinical pneumonia aged 2 months to 5 years of age will be enrolled. Patients will undergo standard of care test and will have blood proteins measured through Luminex®-based immunoassays. Results of this study may ultimately support future development of an accurate point-of-care test for bacterial disease to guide clinicians in choices of treatment and to assist in the prioritization of intensive care in resource-limited settings.

Since their introduction in the late 90's, rapid diagnostic tests (RDTs) have markedly improved our ability to control malaria; yet they have inherent limitations which include low sensitivity in Plasmodium vivax detection and inability to detect hrp2/3 gene deleted Plasmodium falciparum parasites. In addition, the spread of P. falciparum parasites lacking hrp2 gene jeopardizes the long-term use of P. falciparum-specific HRP2-based RDTs. A partnership between RapiGEN, FIND, and the Bill and Melinda Gates Foundation (BMGF) is addressing these limitations by developing five novel malaria RDTs with improved pLDH and HRP2 detection. RapiGEN has also developed three novel malaria RDTs - BIOCREDIT Malaria Ag Pf/Pv (pLDH/pLDH), BIOCREDIT Malaria Ag Pf (pLDH/HRP2) and BIOCREDIT Malaria Ag Pf (pLDH) - to address these drawbacks. The BIOCREDIT Malaria Ag Pf/Pv (pLDH/pLDH) is a combo test that detects P. falciparum and P. vivax on a single device. BIOCREDIT Malaria Ag Pf (pLDH/HRP2) targets both PfLDH and HRP2 antigens in P. falciparum; and BIOCREDIT Malaria Ag Pf (pLDH) has improved detection of pLDH in P. falciparum. In countries with circulation of hrp2/3 deleted P. falciparum malaria parasites or high P. vivax burden, these improved RDTs may be invaluable in malaria elimination. This study is a prospective and retrospective evaluation of RapiGEN's BIOCREDIT Malaria Ag RDTs in malaria-endemic countries to assess their clinical performance for detection of malaria. The purpose of this study is to provide a high level outline of the study design and conduct to support the collation of a data package for WHO Pre-Qualification proposed study.

Prospective cross-sectional diagnostic accuracy study with 1,000 patient participants and 30 lay provider/health care worker participants. The patient participant population will be recruited at clinics. At the point of care, study staff will collect capillary blood samples and conduct malaria microscopy (both the standard of care and study specific research-grade microscopy) and two index tests: the NxTek™ Malaria P.f plus Rapid Diagnostic Test (RDT) and the NxTek™ Malaria P.f/P.v RDT. Venous blood will be collected and transferred to the laboratory where the reference PCR assay and three comparator RDTs will be run. The index RDTs will also be repeated in the laboratory. All clinical management of study participants will follow the standard of care for malaria diagnosis in Brazil and will be based on the standard microscopy result. Confirmatory testing may also be conducted, such as typing and sequencing of Plasmodium genes and antigens of interest, including but not limited to HRP2, HRP3, and pLDH as well as the human inflammatory response marker CRP. The lay provider/health worker participants will include intended users of the index tests. They will be surveyed to assess index test usability through a questionnaire to assess label and packaging comprehension as well as results interpretation.

Historically, Plasmodium vivax has been termed "benign" due to its non-life threatening clinical course and since the 1800's this view has been cultivated as demonstrated by the use of the term "benign tertian malaria" to describe the infection.However over the last 15 years, more severe P. vivax malaria is being reported, causing concern that severe P. vivax malaria is under diagnosed. The definition of severe P. vivax malaria borrows from P. falciparum and is primarily one of exclusion. Species PCR (polymerase chain reaction) is the only way to prove P. vivax mono-infection but is expensive and requires skilled staff and technology. In resource constrained settings, diagnostic testing is not available for detection of most non-malarial infections further affecting the ability to determine whether severe symptoms are due to P. vivax malarial infection or a concomitant one. Retrospective studies from India, Pakistan, Indonesia, Papua New Guinea and Sudan support the existence of severe P. vivax malaria. However, inconsistent methodologies, definitions of severity, and use of diagnostic tests to exclude concomitant infection do not allow for standardised assessments for severe P. vivax infection across studies. A review by Baird, highlighted that the risk of being classed as suffering from severe illness was only minimally higher in P. falciparum than in P. vivax, but was unable to combine the data as a meta-analysis. The primary reported symptoms for severe P. vivax included severe anaemia particularly in children, severe thrombocytopaenia, respiratory distress, neurological syndromes (coma or seizures), renal and hepatic failure. Prospective studies have shown similar results. Tjitra et al showed that 23% (675 of 2,937) patients admitted with microscopically diagnosed P. vivax infections in Papua, Indonesia had severe disease and that the risk of severe malaria was significantly higher when admitted with P. vivax than with P. falciparum. In studies from Papua New Guinea, few differences between the clinical presentation of P. falciparum and P. vivax were found in children with severe malaria. This appears to be similar in populations from Sudan, Pakistan and India. In contrast, in Thailand, anecdotal observations note a low prevalence of severe P. vivax infections. The WHO criteria to assess severe P. falciparum have been extrapolated to P. vivax. In the 2015 WHO malaria guidelines some criteria now account for P. vivax, such as removing a minimum parasitaemia when assessing for severe anaemia. Whilst these criteria may not be the most sensitive tool to define severe P. vivax infections, it is used for this purpose. It has been suggested that additional clinical information may be necessary to define truly severe P. vivax cases. In order to describe the characteristics of the severity of P. vivax infections in north-western Thailand, we will perform a retrospective review of annual reports of the outpatient database, the inpatient database and eligible inpatient medical records from 2001 to 2016. The WHO malaria guidelines and additional clinical information will be used to assess the severity of infection and thus, a rate of severe P. vivax can be determined.

Longitudinal survey in Northern Senegal to investigate the environmental factors modulating the immune response to childhood vaccines and to malaria. A cohort of 410 children aged 1 to 10 from 5 villages of the Senegal River Valley(Podor District) was followed-up for 18 months. During that period, 5 visits have been made to the villages to assess the immunological and nutritional status of the children.

This is a study of the genetics of malaria transmission by the mosquito vector in Africa, Anopheles gambiae. The study focuses on the mosquito vector, not the human subjects infected with malaria. DNA extracted from infected mosquitoes will be analyzed genetically by microsatellite and single-nucleotide polymorphisms (SNPs) to identify mosquito genes that control mosquito resistance to malaria parasites.